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The recent histories of South Africa and Brazil share many commonalities. Most obviously, both have experienced a shared political history of democratic transition. Two somewhat similar forms of socio-political oppression and manipulation - military rule in Brazil (ended 1985) and South African apartheid (ended 1994) - have been replaced by democratic regimes and exceedingly optimistic hopes for the future. Yet neither transition has been as smooth as expected. Consequently, a liminal situation has been created, where past and present discourses compete for space. This has recently been explored in each country's respective literatures: K. Sello Duiker's The Quiet Violence of Dreams and Rodrigo de Souza Leão's All Dogs Are Blue are just two examples. This article will explore the common theme of madness in these novels to highlight liminality. In particular, I argue that the treatment of insanity denies the patient's individuality and replicates the identity politics of the colonial situation. This, I suggest, reveals how postcolonial modernity in Brazil and South Africa relies on a continuing and normalised psycho-politics of otherness. Further, I will consider questions revolving around language, reliability and everyday emotions, focusing on the uncomfortable juxtaposition of global, national and local in both countries as they struggle to enter the modern world order. Ultimately, the only way we can alleviate madness and harness the social benefits of modernity and globalisation comes through accepting difference and understanding the specific individual circumstances of those we call 'mad'.

Angifi Dladla is a Poet of No Sure Place. His poetry speaks for the marginalized and explores the otherwise unmentioned dynamics of South Africa's political and social landscape. In this article I explore how this label is demonstrated within his two collections of poetry, The Girl Who Then Feared to Sleep and Lament for Kofifi Machu. More specifically, my argument engages with the evolving meanings of freedom evoked by Dladla, first in his apartheid-era poetry and, second, in that of today's post-apartheid situation. I demonstrate how the black-on-black violence of the 1980s townships caused a sense of confinement that forced Dladla within himself. Only then was he able to understand freedom and chart a way forward. Following this, the article turns toward those poems that depict contemporary South Africa. My analysis suggests that when freedom, not oppression, is the official political environment of the day, the reality for many is only continued violence and despair. To chart a way out of this bleak malaise, Dladla exhorts others to write in the style of his own poetry.

This article aims to reassess recent and continuing analyses of Soweto poetry that merely confirm it as a product and expression of a Black Consciousness vogue. Discussing works by Mongane Serote, Sipho Sepamla, James Matthews and Njabulo Ndebele, I argue that although Black Consciousness ideas of self-respect and self-assertion are unmistakably included, this canon is situated within a profoundly complex historical and social context. Adopting Steve Biko's alternative definition of a 'national culture', I argue that Soweto poetry is a medial literature. This oeuvre creates a dialogue between common binary constructions of race, agency, culture and locale, and therefore becomes a factor in the creation of Black Consciousness and not simply its reflection.

Going as far as to discuss political violence and funerals alongside poetry and theatre, this article adopts an inclusive approach to culture and explores the changing nature of performance in 1980s South Africa. Focusing initially on trade unions and worker culture, before widening the discussion, it is shown that those marginalized by apartheid society were able to work at the boundaries of established genres to perform messages of mobilization that simultaneously created temporarily liberated areas inscribed with new forms of authority and agency. The article considers poetry by Alfred Qabula and Mzwakhe Mbuli; new developments in theatre; and political events and argues that each, by blurring the distinction between the performer and the audience, similarly acted as popular tools of communication. They replaced the literary imaginary of previous decades and created new public spaces.

Starting from a reading of Damon Galgut's The Good Doctor, this article examines the changing nature of social space in South Africa since 1994 as reflected in recent writing by Galgut, Ivan Vladislavić, Jonny Steinberg, K.S. Duiker and J.M. Coetzee. Adapting Mikael Karlström's distinction between 'dystopian' and 'eutopian' responses to social phenomena, I argue that post-apartheid literature bears witness to the perpetuation of a fundamentally dystopian society. South Africa, by these lights, has seen no significant opening up and making public of space either physically or otherwise. Discussing the urban environment, crime, xenophobia, gender relations and sexuality, the article shows that power remains in the private sphere, with space still constructed in terms of exclusion rather than inclusion.

BackgroundOX40 has been widely studied as a target for immunotherapy with agonist antibodies taken forward into clinical trials for cancer where they are yet to show substantial efficacy. Here, we investigated potential mechanisms of action of anti-mouse (m) OX40 and anti-human (h) OX40 antibodies, including a clinically relevant monoclonal antibody (mAb) (GSK3174998) and evaluated how isotype can alter those mechanisms with the aim to develop improved antibodies for use in rational combination treatments for cancer.MethodsAnti-mOX40 and anti-hOX40 mAbs were evaluated in a number of in vivo models, including an OT-I adoptive transfer immunization model in hOX40 knock-in (KI) mice and syngeneic tumor models. The impact of FcγR engagement was evaluated in hOX40 KI mice deficient for Fc gamma receptors (FcγR). Additionally, combination studies using anti-mouse programmed cell death protein-1 (mPD-1) were assessed. In vitro experiments using peripheral blood mononuclear cells (PBMCs) examining possible anti-hOX40 mAb mechanisms of action were also performed.ResultsIsotype variants of the clinically relevant mAb GSK3174998 showed immunomodulatory effects that differed in mechanism; mIgG1 mediated direct T-cell agonism while mIgG2a acted indirectly, likely through depletion of regulatory T cells (Tregs) via activating FcγRs. In both the OT-I and EG.7-OVA models, hIgG1 was the most effective human isotype, capable of acting both directly and through Treg depletion. The anti-hOX40 hIgG1 synergized with anti-mPD-1 to improve therapeutic outcomes in the EG.7-OVA model. Finally, in vitro assays with human peripheral blood mononuclear cells (hPBMCs), anti-hOX40 hIgG1 also showed the potential for T-cell stimulation and Treg depletion.ConclusionsThese findings underline the importance of understanding the role of isotype in the mechanism of action of therapeutic mAbs. As an hIgG1, the anti-hOX40 mAb can elicit multiple mechanisms of action that could aid or hinder therapeutic outcomes, dependent on the microenvironment. This should be considered when designing potential combinatorial partners and their FcγR requirements to achieve maximal benefit and improvement of patient outcomes.

Key summary points Aim To determine the prevalence of frailty among older people attending emergency care. Findings Across 14 European countries, 40% of older people using emergency care were living with at least mild frailty. 14% of all adult users were older people with frailty. Message The high prevalence of frailty in emergency care indicates the need to accordingly configure healthcare systems and plan workforces. Introduction Current emergency care systems are not optimized to respond to multiple and complex problems associated with frailty. Services may require reconfiguration to effectively deliver comprehensive frailty care, yet its prevalence and variation are poorly understood. This study primarily determined the prevalence of frailty among older people attending emergency care. Methods This cross-sectional study used a flash mob approach to collect observational European emergency care data over a 24-h period (04 July 2023). Sites were identified through the European Task Force for Geriatric Emergency Medicine collaboration and social media. Data were collected for all individuals aged 65 + who attended emergency care, and for all adults aged 18 + at a subset of sites. Variables included demographics, Clinical Frailty Scale (CFS), vital signs, and disposition. European and national frailty prevalence was determined with proportions with each CFS level and with dichotomized CFS 5 + (mild or more severe frailty). Results Sixty-two sites in fourteen European countries recruited five thousand seven hundred eighty-five individuals. 40% of 3479 older people had at least mild frailty, with countries ranging from 26 to 51%. They had median age 77 (IQR, 13) years and 53% were female. Across 22 sites observing all adult attenders, older people living with frailty comprised 14%. Conclusion 40% of older people using European emergency care had CFS 5 + . Frailty prevalence varied widely among European care systems. These differences likely reflected entrance selection and provide windows of opportunity for system configuration and workforce planning.

Background Smoking status, alcohol consumption and HPV infection (acquired through sexual activity) are the predominant risk factors for oropharyngeal cancer and are thought to alter the prognosis of the disease. Here, we conducted single-site and differentially methylated region (DMR) epigenome-wide association studies (EWAS) of these factors, in addition to ∼ 3-year survival, using Illumina Methylation EPIC DNA methylation profiles from whole blood in 409 individuals as part of the Head and Neck 5000 (HN5000) study. Overlapping sites between each factor and survival were then assessed using two-step Mendelian randomization to assess whether methylation at these positions causally affected survival. Results Using the MethylationEPIC array in an OPC dataset, we found novel CpG associations with smoking, alcohol consumption and ~ 3-year survival. We found no CpG associations below our multiple testing threshold associated with HPV16 E6 serological response (used as a proxy for HPV infection). CpG site associations below our multiple-testing threshold ( P Bonferroni < 0.05) for both a prognostic factor and survival were observed at four gene regions: SPEG (smoking), GFI1 (smoking), PPT2 (smoking) and KHDC3L (alcohol consumption). Evidence for a causal effect of DNA methylation on survival was only observed in the SPEG gene region (HR per SD increase in methylation score 1.28, 95% CI 1.14 to 1.43, P 2.12 × 10 −05 ). Conclusions Part of the effect of smoking on survival in those with oropharyngeal cancer may be mediated by methylation at the SPEG gene locus. Replication in data from independent datasets and data from HN5000 with longer follow-up times is needed to confirm these findings.

We calculate financial risk profiles for representative vineyards of 50-ha in four wine grape regions of South Australia using straw or living mulches as alternatives to herbicides for under-vine management. Calculations are based on replicated experiments in a commercial vineyard in each district with the most widely grown vine variety of each; the grape yields were measured in 2016 and 2017. Published district grape prices and yields for the years 2006 through 2017 form the basis for novel stochastic analysis. The herbicide (Control) treatment in Barossa Shiraz (BS) and Riverland Merlot (RM) showed greater median Gross Revenues (prices x yields) than the other two districts: Eden Valley Shiraz and Langhorne Creek Cab-Sav. After subtraction of operating costs, and assuming alternative treatments produce grapes of equal quality and price as the Control in a district, the alternatives gave median Gross Margins ( $/ha) greater than the Control in BS but lower than the Control in RM. Gross Margin results were mixed in the other two districts. The Gross Margin results above are magnified in financial Risk Profiles based on variations in Gross Margins times 50 ha across multiple ten-year periods after subtracting taxes, drawings, recurrent capital costs and interest on accumulating debt, for decadal cash margins. The Risk Profile of a treatment in a district is its cumulative distribution of decadal cash margins ($ M). We show that choice of under-vine treatment can significantly affect a vineyard's financial viability.